Time-Dependent Effects of Cryoablation for Renal Tumor on Overall and Split Renal Function

Purpose

To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney.

The impact of musculoskeletal diseases on the presence of locomotive syndrome

Objectives: We assessed the impact of musculoskeletal diseases, depressive mental state, and hypertension on locomotive syndrome, a condition of reduced mobility requiring nursing care. Since locomotive syndrome is a major public health issue that needs attention, its relationship with functional inconvenience in performing daily activities was also investigated.

Methods: We conducted a cross-sectional study using an Internet panel survey, comprising 747 persons aged 30–90 years. Demographics, personal medical history, and daily activity data were assessed. The 25-question Geriatric Locomotive Function Scale was used to diagnose locomotive syndrome. Stepwise linear regression analysis and logistic regression analysis were conducted to evaluate the association between locomotive syndrome, musculoskeletal diseases, and functional inconvenience.

Results: Aging, osteoporosis, and low back pain significantly increased the risk of locomotive syndrome, followed by knee osteoarthritis and lumbar spinal stenosis. Locomotive syndrome was significantly related to depressive mental state and hypertension, and led to functional inconvenience in Seiza sitting, cleaning, shopping, and strolling.

Conclusion: Locomotive syndrome was associated with functional inconvenience in performing common daily activities involving the lower extremities and spine. Osteoporosis and aging were significantly associated with locomotive syndrome. The risk of locomotive syndrome may be decreased by treating comorbid osteoporosis and instituting exercise and diet-related modifications.     

Risk factors for pneumothorax associated with isolated congenital diaphragmatic hernia: results of a Japanese multicenter study

This study aimed to elucidate the clinical characteristics of neonates with congenital diaphragmatic hernia (CDH) associated with pneumothorax and evaluate the risk factors for the development of pneumothorax. A retrospective cohort study was conducted in the 15 institutions participating in the Japanese CDH Study Group. A total of 495 neonates with isolated CDH who were born between 2011 and 2018 were analyzed in this study. Among the 495 neonates with isolated CDH, 52 (10.5%) developed pneumothorax. Eighteen (34.6%) patients developed pneumothorax before surgery, while 34 (65.4%) developed pneumothorax after surgery. The log-rank test showed that the cumulative survival rate was significantly lower in patients with pneumothorax than in those without pneumothorax. Univariate analysis revealed significant differences between patients with pneumothorax and those without pneumothorax with regard to the best oxygenation index within 24 h after birth, mean airway pressure (MAP) higher than 16 cmH2O, diaphragmatic defect size, and need for patch closure. Multiple logistic regression analysis indicated that only the MAP was associated with an increased risk of pneumothorax. The cumulative survival rate was significantly lower in isolated CDH patients with pneumothorax than in those without pneumothorax. A higher MAP was a risk factor for pneumothorax in CDH patients.     

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na⁺-Cl⁻ cotransporter (NCC) and Na⁺-K⁺-2Cl⁻ cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.